Role of ER? in Mediating Female Uterine Transcriptional Responses to IGF1.

ABSTRACT: Estrogen (E2) signaling through its nuclear receptor, E2 receptor ? (ER?) increases insulinlike growth factor 1 (IGF1) in the rodent uterus, which then initiates further signals via the IGF1 receptor. Directly administering IGF1 results in similar biological and transcriptional uterine responses. Our studies using global ER?-null mice demonstrated a loss of uterine biological responses of the uterus to E2 or IGF1 treatment, while maintaining transcriptional responses to IGF1. To address this discrepancy in the need for uterine ER? in mediating the IGF1 transcriptional vs growth responses, we assessed the IGF1 transcriptional responses in PgrCre+Esr1f/f (called ER?UtcKO) mice, which selectively lack ER? in progesterone receptor (PGR) expressing cells, including all uterine cells, while maintaining ER? expression in other tissues and cells that do not express Pgr. Additionally, we profiled IGF1-induced ER? binding sites in uterine chromatin using chromatin immunoprecipitation sequencing. Herein, we explore the transcriptional and molecular signaling that underlies our findings to refine our understanding of uterine IGF1 signaling and identify ER?-mediated and ER?-independent uterine transcriptional responses. Defining these mechanisms in vivo in whole tissue and animal contexts provides details of nuclear receptor mediated mechanisms that impact biological systems and have potential applicability to reproductive processes of humans, livestock and wildlife.

SUBMITTER: Hewitt SC 

PROVIDER: S-EPMC5551553 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature